6Q2O

Cryo-EM structure of RET/GFRa2/NRTN extracellular complex. The 3D refinement was applied with C2 symmetry.

6Q2O の概要

• エントリーDOI: 10.2210/pdb6q2o/pdb
• EMDBエントリー: 20576
• 分子名称: Neurturin, GDNF family receptor alpha-2, Proto-oncogene tyrosine-protein kinase receptor Ret, ... (5 entities in total)
• 機能のキーワード: ret, receptor tyrosine kinase, cryo-em, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 243734.82

構造登録者

Li, J.,Shang, G.J.,Chen, Y.J.,Brautigam, C.A.,Liou, J.,Zhang, X.W.,Bai, X.C. (登録日: 2019-08-08, 公開日: 2019-10-02, 最終更新日: 2024-10-23)

主引用文献

Li, J.,Shang, G.,Chen, Y.J.,Brautigam, C.A.,Liou, J.,Zhang, X.,Bai, X.C.
Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands.
Elife, 8:-, 2019

PubMed Abstract: RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands.

PubMed: 31535977
DOI: 10.7554/eLife.47650

実験手法

ELECTRON MICROSCOPY (3.65 Å)